Targeting functionalized nanoparticles to activated endothelial cells under high wall shear stress

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Endothelial inflammation is linked to cardiovascular diseases.
• Vascular-targeted carriers (VTCs) aim to deliver therapeutics to diseased vasculature.
• High shear stress conditions are relevant in vascular narrowing and arteriogenesis.

Purpose of the Study:

• To design and evaluate functionalized nanoparticles (NPs) as VTCs for targeting inflamed endothelium under high shear stress.
• To investigate the adhesion of NPs functionalized with E-selectin binding peptide (Esbp) and anti-ICAM-1 antibody.

Main Methods:

• Carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands.
• In vitro study using microfluidic models with inflamed (TNF-α stimulated) and control endothelial cells (ECs).
• Real-time confocal microscopy monitored NP adhesion under wall shear stresses (40-300 dyne/cm²).

Main Results:

• Functionalized NPs showed significantly higher specific adhesion to activated ECs across tested shear stresses.
• Particle adhesion increased with higher surface coating density (~10,000 molecules/particle).
• Adhesion was shear-dependent, demonstrating targeted localization under pathological flow conditions.

Conclusions:

• Functionalized NPs can be engineered for specific targeting of inflamed endothelial cells under high shear stress.
• These VTCs demonstrate potential for localized drug delivery in conditions like vasoconstriction and arteriogenesis.
• The study highlights the efficacy of ligand-functionalized NPs in mimicking in vivo vascular targeting.